It has long been known that pleomorphism and hyperactivity of the nucleolus is a major characteristic of cancer cells. These observations prompted studies to determine if tumor nucleoli possess components that are absent from nucleoli of normal cells. After a number of studies using polyclonal antisera to tumor nucleoli demonstrated antigenic differences between tumor and normal tissue nucleoli, efforts are made to purify and characterize specific tumor associated nucleolar antigens.
Chan et al. (Transplant Proc. 8: 1955-1957 (1981); Cancer Res. 40: 3194-3201 (1980); J. Cancer Research Clin. Oncol. 103: 7-16 (1981)) and Takahashi et al. (J. Cancer Res. Clin. Oncol. 105: 67-75 (1983)) purified nucleolar proteins with molecular weights of 54, 61 and 68 kD from rat and human tumors that were not found in normal tissues. A nucleolar antigen, p145, was found to be associated with proliferating cells (Freeman et al., Cancer. Res. 46: 3593-98 (1986)). The p145 nucleolar antigen was found in a broad range of human tumors but was not detected in most normal resting tissues.
Studies by others (Bravo et al., Exp. Cell Res. 136: 311-315 (1981); Celis et al., Leukemia Res. 10: 237-249 (1986); Chan et al., Cell Biol. Int. Rep. 9: 61-68 (1985); Mathews et al., Nature 309: 374-376 (1983); Smetana et al., Blut 46: 133-141 (1983); Smetana et al., U.S. Pat. No. 4,448,890; Tan, E. M. Adv. Immunol. 33: 167-240 (1982)) using human autoimmune sera detected nuclear and nucleolar antigens in tumor cells and normal growing cells that were not found in normal resting tissues. These antigens are referred to as "proliferating cells nuclear antigens". The best characterized "proliferating cell nuclear antigen" is a 36 kD antigen termed "Cyclin".